Etiologic diagnosis of acute febrile illnesses should be broad and unbiased. These illnesses, often present with vague symptoms, are caused by a myriad of potential pathogens, some emerging or unanticipated, all of which vary by geographic region. Unfortunately, accurate diagnosis of the causative pathogen(s) can be compromised by diagnostic assays biased to target a pre-determined set of microorganisms. Broad differential diagnostics to rapidly identify unknown pathogen(s) within the acute-care timescale would enable early fine-tuning of antibiotic stewardship according to local susceptibility profiles and reduce patient morbidity and mortality.